Tetrahydro-2-(nitromethylene)-2H-1,3-thiazine insect control agents

ABSTRACT

Novel insecticidal tetrahydro-2-(nitromethylene)-2H-1,3-thiazines.

This application is a continuation-in-part of application Ser. No.554,361, filed Mar. 3, 1975, now abandoned, which is acontinuation-in-part of application Ser. No. 468,124, filed May 8, 1974,now abandoned.

DESCRIPTION OF THE INVENTION

It has been found that useful insecticidal activity is possessed bycertain tetrahydro-2-(nitromethylene)-2H-1,3-thiazines. These compoundshave been found to be resonance hybrids, the principal formscontributing thereto being described by the formulae: ##STR1## whereinthe symbols have the respective meanings set out hereinafter. When thesymbol, R, represents a hydrogen atom, the resonance hybrid also mayexist in two tautomeric forms, one form being the resonance hybriddescribed above and the other being represented by the formula ##STR2##This form, C, can be designated as a 2-(R¹-nitromethyl)-5,6-dihydro-4H-1,3-thiazine. The left-hand form of theresonance hybrid (i.e., form A) can be designated as a3-R-tetrahydro-2-(nitromethylene)-2H-1,3-thiazine, while the right-handform of the hybrid (i.e., form B) can be designated as a3-R-2-(aci-nitromethyl)-5,6-dihydro-4H-1,3-thiazinium hydroxide innersalt.

The resonance hybrid may exist as either of two geometric (cis-trans)isomers, depending upon the spatial relationship of the moieties aboutthe bond between the carbon atom of the nitromethylene moiety and thering carbon atom to which it is joined.

In this specification, for the sake of simplicity, these compounds willbe referred to generally astetrahydro-2-(nitromethylene)-2H-1,3-thiazines. This terminology isintended to include all of the contributors to the resonance hybrid, thegeometric isomers, and the tautomers, as well as mixtures thereof.

In these compounds, the symbols used in the formulae having thefollowing meanings, respectively:

R is hydrogen, alkyl, alkenyl, alkoxyalkyl, cycloalkylalkyl, cyanoalkyl,haloalkenyl, aralkyl or alkoxycarbonylvinyl.

R¹ is hydrogen or alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,halo(hydroxy)alkyl, alkoxyalkyl, cyanoalkyl, hydroxyalkyl,alkoxycarbonylalkyl, alkylcarbonylalkyl, alkylthioalkyl,alkylsulfinylalkyl, aryl, aralkyl or arylthio optionally substituted onthe ring by one or more of halogen, nitro, cyano, alkyl, aryl, alkoxy oraryloxy; halogen; aminomethyl, --CH₂ --NR² R³, R² is alkyl,hydroxyalkyl, alkoxyalkyl, cycloalkyl, alkenyl, aryl, haloaryl, oraralkyl, and R³ is hydrogen or one of the moieties represented by R² ;--CH₂)_(n) R⁴, wherein n is zero, one or two, and R⁴ is aheteromonocyclic moiety of from five to six atoms in the ring,containing in the ring carbon atoms and one to two of oxygen (--O--),sulfur (--S--) or nitrogen (═N-- or --NH--) bonded to carbon in thering; or is ##STR3##

In all cases, each alkyl, cycloalkyl, alkenyl, alkynyl or alkylenemoiety suitably contains no more than eight and preferably no more thanfour carbon atoms and each may be of straight-chain or branched-chainconfiguration.

The preferred aryl moieties are optionally substituted phenyl. Thepreferred aminoalkyl moieties are dialkylaminomethyl. The preferredaralkyl moieties are optionally-substituted phenylmethyl. Preferredheterocyclic (R⁴) moieties are furanyl, tetrahydrofuranyl, dioxolanyl,thienyl, thiopyranyl, pyridinyl, pyrrolidinyl and morpholinyl, and theirR⁴ -methyl- counterparts.

Also, when R is hydrogen, the invention includes salts of that subclassof compounds -- i.e., R is a cationic species. The contemplated saltsare alkali metal salts, alkyl halide salts, ammonium salts and aminesalts generally, and particularly salts of alkyl- and alkanolamines, andpolyamines. Included are the salts of mono-, di- and trialkyl, alkanol,alkenyl and mono- and poly- (alkoxy)alkylamines, and polyamines in whicheach alkyl, alkenyl, alkanol, or alkoxyalkyl moiety contains from one to20 carbon atoms or more including, but not necessarily limited to, oneor more of dimethylamine, diethanolamine, trimethylamine, oleylpropylenediamine, n-dodecylamine, n-tetradecylamine, n-hexadecylamine,n-octadecylamine, heptylamine, triethanolamine, tert-C₁₁₋₁₄ andtert-C₁₈₋₂₄ primary amines, oleylamine, coco amine, hydrogenated tallowamine, tallow amine, soya amine, dicoco amine and di(hydrogenatedtallow) amines, dimethyl hexadecylamine, dimethyl octadecylamine,dimethyl coco amine, dimethyl soya amine, N-coco propylenediamine,N-soya propylenediamine, N-tallow propylenediamine, and the like.

Of particular interest because of the activity of the members thereof isthe sub-class of this genus of compounds wherein R is hydrogen.

For illustration, preparation of typical species of the genus isdescribed in the examples included hereinafter. Other typical,illustrative species of this genus oftetrahydro-2-(nitromethylene)-2H-1,3-thiazines include those wherein thesymbols represent the following moieties, this manner of naming thesespecies being accurate, yet pointing out the differences between thedifferent species more clearly than if the entire, complicated name ofeach species were to be given:

R¹ = h, r =

2-propenyl

3-chloro-2-propenyl

2-cyanoethyl

methoxymethyl

2-(cyclohexyl)ethyl

cyclopropylmethyl

R = h, r¹ =

methyl

2-hydroxyethyl

methoxymethyl

(methylthio)methyl

methoxycarbonylmethyl

2-propynyl

3-chloro-2-propenyl

(dipropylamino)methyl

(bis(2-hydroxyethyl)amino)methyl

(bis(2-methoxyethyl)amino)methyl

dicyclohexylaminomethyl

(diphenylamino)methyl

R¹ = (dimethylamino)methyl, R =

methyl

2-chloro-2-propenyl

R¹ = 2-propenyl, R =

methyl

Compounds of this invention can be prepared by several generalprocedures:

Method A: treating a nitroketene dimethyl mercaptole (NKDM) (R. Gompper& H. Schaefer, Berichte, 100, 591 (1967)) with a 3-amino-1-propanethiol(S. D. Turk, et al., J. Org. Chem., 27, 2846 (1962)), including suitablysubstituted 3-amino-1-propanethiols, referring to the definitions of Rand R².

Method B: treating 5,6-dihydro-2-(methylthio)-4-H-1,3-thiazine (A. F.McKay et al., J. Am. Chem. Soc., 80, 3339 (1958)) with an alkylnitroacetate (S. Zen, et al., Kogyo Kagaku Zasshi, 74, 70 (1971)) in thepresence of a catalytic amount of zinc ion (e.g., zinc chloride) to formthe alkyl nitro(tetrahydro-2H-1,3-thiazine-2-ylidene)acetate, which ishydrolyzed with a base and decarboxylated by acidification to give thedesired product.

Method C: substituting a moiety, R, on the ring nitrogen atom bytreating tetrahydro-2-(nitromethylene)-2H-1,3-thiazine, which can beprepared by either of Methods A or B with a strong alkali metal base ina liquid mixture of tetrahydrofuran and hexamethylphosphoramide, or withan alkali metal derivative of the appropriate alcohol in an alcohol assolvent, then treating the resulting intermediate with the appropriateR-sulfate, iodide, chloride, bromide or tosylate.

Method D: involves a Michael Reaction wherein the nitromethylenethiazine is treated with a compound containing an activated olefinicdouble bond which will react at the alpha carbon atom of the thiazine.This method is illustrated in Examples 9, 11 and 12 hereinafter.

Method E: compounds of this invention wherein R¹ is halogen can beprepared by direct halogenation, by elemental halogen or by ahalogenated compound containing positive halogen, of the appropriate R =H precursor.

Method F: 5,6-dihydro-2-(methylthio)-4H-1,3-thiazine is treated with anappropriate alkylating agent in an aprotic high dielectric constantsolvent, and the product is treated with nitromethylpotassium in aprotic high dielectric constant solvent.

Method G: tetrahydro-2-(nitromethylene)-2H-1,3-thiazine is heated with asuitably reactive alkylating agent, without or with a suitable solvent.

Method H: tetrahydro-2-(nitromethylene)-2H-1,3-thiazine is treated witha reactive aldehyde in a suitable solvent, the product being isolatedand purified by conventional techniques.

Method I: involves a Mannich Reaction, whereintetrahydro-2-(nitromethylene)-2H-1,3-thiazine is treated with asecondary amine or with a dihaloaniline with the resulting mixture beingtreated with formaldehyde to form the substituted aminomethylnitromethylenethiazine.

Method J: Compounds of the invention wherein R¹ is --CH₂ --NR² R³ can beprepared by treating2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethanol (R¹ = --CH₂ OH)with the appropriate amine, H--NR² R³.

Method A is carried out by mixing the reactants in a suitable liquidmedium such as a lower alkanol. The reaction can in some cases becarried out at essentially room temperature while in other cases gentleto moderate heating (up to 100° C) may be required. Generally, it willbe found best to employ a slight to moderate excess (5-25%) of the thiolover that theoretically required to react with the mercaptole. For bestresults, oxygen should be excluded from the reaction zone by conductingthe reaction in a nitrogen atmosphere. The product can be recovered byremoving the solvent, digesting the residue with water and thenextracting the desired product from the aqueous phase by means of asuitable solvent such as methylene chloride.

Method B can be conducted by gradually treating the thiazine with aslight to moderate (5-20%) excess of the alkyl nitroacetate at amoderately elevated temperature, e.g. 80°-130° C, in the presence of acatalytic amount of zinc ion which conveniently is supplied as zincchloride, to form the thiazine acetate intermediate. While a suitablesolvent may be used, in some cases at least, one will not be required.The product can be worked up by conventional extraction andcrystallization techniques. The acetate then is decarboxylated bytreatment (hydrolysis) with excess base, followed by neutralization ofthe mixture and recovery of the product. The hydrolysis can be effectedat room temperature or at slight to moderately elevated temperatures.Product work-up again can be effected by conventional filtration,extraction, crystallization and elution (chromatographic) techniques.

In method C the thiazine is substituted on the ring nitrogen atom bytreating the thiazine with about an equimolar amount of a strong alkalimetal base in a suitable liquid reaction medium at room temperature orat a slight to moderately elevated temperature, then treating theresulting mixture with about the theoretical amount of the sulfate,iodide, bromide, chloride or tosylate of the moiety, R, to besubstituted on the nitrogen atom of the thiazine ring. This lattertreatment preferably is conducted at temperatures below roomtemperature, for example, at 0°-15° C. The base used may be, forexample, sodium, potassium or lithium hydrides, their hydroxides, orlower alkyls or alkoxides. A suitable liquid reaction medium for usewith the metal hydride, alkyl or hydroxide thereof istetrahydrofuran/hexamethylphosphoramide mixture. Where an alkoxide isused, it preferably is tertiary-butoxide and the solvent is tertiarybutyl alcohol. In many cases, at least, it will not be necessary toisolate the intermediate product -- the crude reaction mixturecontaining it may be treated with the R-sulfate, -iodide, -bromide,-chloride or -tosylate.

As has been indicated, most of the reactions should be conducted in anitrogen atmosphere, and the techniques for recovery and purification ofthe intermediate and final products from the crude reaction mixtures areconventional and are illustrated in the examples indicated hereinafter.

Method D is carried out by heating a mixture of the thiazine and theolefinic compound in a suitable solvent at a moderately elevatedtemperature, for example, 60°-100° C. Suitable solvents includehalogenated alkanes. Conduct of the reaction in 1,2-dichloroethane atits boiling point (refluxing at 83°-84° C) often is convenient.

In Method E, the thiazine compound (R = H), optionally in solution in asuitable solvent, optionally in the presence of a hydrogen halideacceptor, is treated with an equimolar quantity of a halogen or of apositive halogenating agent. Suitable positive halogenating agents areany of the conventional halogenating agents in which the halogen has apositive character, such as N-chloro- and N-bromosuccinimide. Water isordinarily suitable and convenient as the solvent when chlorine orbromine is used as the halogenating agent. When a positive halogenatingagent is used, the lower haloalkanes are suitable solvents. The reactionordinarily can be effected under mild conditions, e.g., 0° C to about45° C. To avoid di-halogenation, it is usually desirable to employ atemperature of the range of 5°-10° C and add the halogen slowly withvigorous stirring to avoid local excess of the halogen.

In Method F, the suitable alkylating agents include, for example, alkylhalides, sulfates, and tosylates. Suitable solvents includedimethylformamide, dimethyl sulfoxide, acetone, acetonitrile,nitrobenzene and sulfolane. The reaction is effected at a temperature offrom about 20° to about 125°. The product can be isolated byprecipitation with an inert solvent, or by concentration under reducedpressure. The nitromethylpotassium is readily prepared by treatingnitromethane with t-butoxide in t-butanol. The reaction of theintermediate with nitromethylpotassium suitably is conducted in asolvent such as t-butanol, and at about room temperature. The product isisolated by dilution of the reaction mixture with water and extractionwith a suitable solvent such as methylene chloride.

In Method G the suitable alkylating agents are those described forMethod F, and the reaction suitably is conducted at a temperature offrom about 50°-150°. If a solvent is used, lower haloalkanes aresuitable.

In Method H, the suitable aldehydes are the haloaldehydes such aschloral, bromal, dichloroacetaldehyde and the like. The reactionproceeds at room temperature although warming may be desirable to insurecompletion of the reaction. Recovery and purification in this case, andin the case of Method G, are accomplished by conventional techniques.

In Method I, the thiazine reactant preferably is mixed with a smallamount of a lower alkanol and the reactions are conducted at about roomtemperature. In some cases it may be necessary to heat the mixture to amoderately elevated temperature -- e.g., about 50° C, to effect thereaction at a reasonable rate.

In Method J, the treatment is carried as described for Method I.Preparation of the precursor alcohol is described in Example 33.

In some cases, the product is non-basic in character so that it will notform a salt with the by-product hydrogen halide even when no acidacceptor is present. In such cases, the desired product can be recoveredby extracting the reaction mixture with a suitable non-water solublesolvent, then evaporating the solvent. Suitable solvents are thehalogenated alkanes such as methylene chloride. Where the product formsthe salt, the product can be recovered by treating the reaction mixturewith a base such as sodium bicarbonate to spring the product, thenrecovering it by solvent extraction of the aqueous mixture with ahalogenated alkane.

Compounds of this invention may also be prepared by other methods, asillustrated in particular cases in the examples following.

All of these methods are illustrated in the following examples. In allcases, the identity of the product and the identity of any intermediateused was confirmed by appropriate analyses.

EXAMPLE 1 Tetrahydro-2-(nitromethylene)-2H-1,3-thiazine (1A) Method A

86.9 g of 3-amino-1-propanethiol was added to a suspension of 132 g ofnitroketene dimethyl mercaptole in 2 liters of ethanol, and the mixturewas stirred at 25° for 18 hours under nitrogen. The resulting solutionwas decanted from a small amount of tarry material and concentratedunder reduced pressure to leave a viscous residue which was digested in2 liters of water with 1 hour of vigorous stirring. The aqueous phasewas separated from solid material, clarified by filtration and extractedwith methylene chloride. The organic extract was dried (sodium sulfate)and concentrated under reduced pressure to give a yellow solid. Thesolid was washed with ether to give 1A as a yellow solid, m.p. 71°-74°.

EXAMPLE 2 Tetrahydro-2-(nitromethylene)-2H-1,3-thiazine (1B) Method BEthyl nitro(tetrahydro-2H-1,3-thiazin-2-ylidene)acetate (2A)

To a mixture of 235 g of 5,6-dihydro-2-(methylthio)-4H-1,3-thiazine and2 g of zinc chloride at approximately 115° in a nitrogen atmosphere, 263g of ethyl nitroacetate was added dropwise over a 1.5 hour period. Themixture was held at 110°-120°. When evolution of methyl mercaptan ceasedafter 45 minutes further stirring of the heated mixture, 1 g of zincchloride was added and the mixture was stirred at about 115° for 1.25hours. An additional 1 g of zinc chloride then was added and stirring ofthe mixture at about 115° was continued for 1.5 hours. The mixture thenwas poured into a cooled solution of 2/1 ether/isopropyl alcoholmixture. The crystallized product was collected, washed with ether anddried under reduced pressure to leave a tan solid, m.p. 100°-102°, whichon recrystallization from methanol gave 2A as a pale yellow solid, m.p.105°-106°.

2.3 g of 2A was added to 10 ml of 20% aqueous sodium hydroxide and themixture was stirred at room temperature for 12 hours. The resultingsolution was treated dropwise with 3.5 g of acetic acid. The additionwas accompanied by vigorous gas evolution. The resulting mixture wasextracted with methylene chloride and the extract was dried (magnesiumsulfate) and concentrated under reduced pressure to give 1B as a paleyellow solid, m.p. 76°-78°.

EXAMPLE 3 Tetrahydro-3-methyl-2-(nitromethylene) (3) -2H-1,3-thiazineMethod C

A solution of 4.8 g of 1B in 30 ml of tetrahydrofuran was added dropwiseto a suspension of oil-free sodium hydride (from 1.35 g of a 57% mineraloil dispersion) in 30 ml of tetrahydrofuran and 10 ml ofhexamethylphosphoramide, with stirring under nitrogen, the mixture beingheld at 23°-25°throughout the addition. Gas evolved. After 30 minutes,the reaction mixture was cooled to 5°-10° and a solution of dimethylsulfate in 25 ml of tetrahydrofuran was added dropwise thereto. Themixture was stirred at 25°-35° for 1 hour, then poured into water andextracted with methylene chloride. The extract was dried (sodiumsulfate) and concentrated under reduced pressure to leave a liquid. Thiswas triturated with ether to give a gummy solid, m.p. 140°-145°.Recrystallization from ethyl acetate gave 3, as a pale yellow solid,m.p. 157°-158.5°.

EXAMPLE 4 2-(bromonitromethylene)-tetrahydro-2H-1,3-thiazine (4) MethodE

A solution of 3.2 g of bromine in 10 ml of methylene chloride was addeddropwise to a solution of 3.2 g of 1B in 50 ml of water, the temperaturebeing held at 5°-10°. The mixture was then stirred for 45 minutes when200 ml of methylene chloride was added to dissolve the solid material.The organic phase was separated, washed with water, dried (sodiumsulfate) and concentrated under reduced pressure to give a yellow solid.This was washed with ether to give 4, as a yellow solid, m.p. 122° (withdecomposition).

EXAMPLES 5 and 6 3-benzyl-tetrahydro-2-(nitromethylene)-2H-1,3-thiazine(5) tetrahydro-2-(1-nitro-2-phenylethylidene)-2H-1,3-thiazine (6) MethodC

A solution of 8.0 g of 1B in 40 ml of tetrahydrofuran was added dropwiseto a suspension of oil-free sodium hydride (from 2.3 g of a 50% oildispersion) in a mixture of 20 ml of tetrahydrofuran and 10 ml ofhexamethylphosphoramide, stirred under nitrogen and maintained at15°-30°. After 45 minutes of stirring, a solution of 9.4 g of benzylbromide in 10 ml of tetrahydrofuran was added dropwise, the temperatureof the mixture being held at 6°-8°. The mixture was stirred for 2 hoursat 25° and 2 hours at reflux temperature, then allowed to stand at roomtemperature overnight. Then 200 ml of ice water was added and theresulting mixture was extracted with methylene chloride, and the extractwas washed with saturated salt solution. The extract was dried (sodiumsulfate) and concentrated under reduced pressure to give 13.4 g of anamber oil. Dry-column chromatography, first on silica gel with a 1:1:2mixture of tetrahydrofuran, ethyl acetate and hexane, and then on silicagel with a 3:5:12 mixture of methylene chloride hexane and ethylacetate, gave two fractions, one an organge solid, m.p.: 109°-113° andone a yellow solid, m.p.: 148°-154°. Recrystallization of the firstfraction from ethyl acetate provided 5, as a yellow solid, m.p.:141.5°-143.5°. Recrystallization of the second fraction from ethylacetate gave 6, as a yellow solid, m.p.: 156°-157.5°.

EXAMPLE 7 Tetrahydro-2-(nitromethyene)-3-propyl-2H-1,3-thiazine (7)Method F

A solution of 19.6 g of 5,6-dihydro-2-(methylthio)-4H-1,3-thiazine and30.0 g of propyl iodide in 50 ml of dimethyl formamide was allowed tostand for 15 hours and then heated on a steam bath for 45 minutes. Thesolution was poured into 750 ml of ether and the oil which settled outwas separated and stripped under high vacuum at 55°-60° to leave anamber oil with appropriate spectral features for the propiodide salt. Asolution of 13.0 g of this oil in 15 ml of methylene chloride was addeddropwise to a suspension of the potassium salt of nitromethane intertiary-butyl alcohol (prepared by treating 5.0 grams of nitromethanewith 4.8 g of potassium tert-butoxide in 30 ml of tert-butyl alcohol at23°-25°). The reaction mixture was stirred at room temperature for 18hours under nitrogen, diluted with 600 ml of methylene chloride, andwashed with water and with saturated salt solution. The organic phasewas dried (sodium sulfate) and concentrated under reduced pressure toleave a slightly gummy yellow-orange solid. This material was boiled in150 ml of ether containing 20 ml of ethyl acetate and the resultingsolid residue was chromatographed on silica gel using the dry-columntechnique. Development with 49:1 ethyl acetate/methanol mixture gave twoprincipal portions. The more polar, a yellow solid, m.p. 130°-144°, waswashed with ether to give a solid identified as 7. The less polarportion (a yellow solid, m.p. 144°-170°) was dissolved in chloroform,the solution was treated with charcoal, filtered and concentrated todryness. The residue was washed with ether to give more 7 as a lightyellow solid, m.p. 159°-161°.

EXAMPLE 8 3-ethyl-tetrahydro-(nitromethylene)-2-H-1,3-thiazine (8)Method F

14.7 g of 5,6-dihydro-2-methylthio-4H-1,3-thiazine was added dropwise toa solution of 62.4 g of ethyl iodide in 100 ml of dimethylformamide at75°. The mixture was stirred for 2 hours under nitrogen at about 75° andthen concentrated under high vacuum to leave a viscous, dark-orangeliquid identified by spectral analyses as3-ethyl-5,6-dihydro-2-methylthio-4H-1,3-thiazinium iodide (8A). Asolution of 27.1 g of 8A in 40 ml of methylene chloride was addeddropwise at 25° to a suspension of nitromethylpotassium (prepared from11.2 g of potassium tert-butoxide and 13 g of nitromethane intert-butanol). The reaction mixture was stirred under nitrogen for 18hr. at 25°, then diluted with 600 ml of methylene chloride. The organicphase was washed with water and with saturated salt solution, dried(sodium sulfate) and concentrated under reduced pressure to leave agummy, yellow solid, m.p.: 75°-80°. This solid was heated for one hourin ether, then the solid residue was separated, being orange-yellow incolor, m.p.: 120°-138°. Chromatography on silica gel using a 1:1:2mixture of tetrahydrofuran/ethyl acetate/hexane as eluent followed bytrituration of the product with ether gave 8 as a light yellow solid,m.p.: 156°-161°.

EXAMPLE 9 5-nitro-5-(tetrahydro-2H-1,3-thiazin-2-ylidene)-2-pentanone(9) Method D

Under a nitrogen atmosphere, 1.9 g of methyl vinyl ketone was addeddropwise to a solution of 4.0 g of 1B in 10 ml of methylene chloride at25°. After stirring for 72 hours, the mixture was concentrated underreduced pressure to give a pale-yellow solid which was washed with etherand dried to give 9, m.p.: 118°-120°.

EXAMPLE 10 2-(chloronitromethylene)-tetrahydro-2H-1,3-thiazine (10)Method E

A mixture 16.0 g of 1B and 13.4 g of N-chlorosuccinimide in 250 ml ofcarbon tetrahcloride was stirred at room temperature for 21 hours. Theresulting mixture was filtered and the solids were extracted withmethylene chloride. The organic liquid phase was washed with water,dried (magnesium sulfate) and concentrated under reduced pressure toleave an orange-yellow solid, chromatography on silica gel with a 1:1methylene chloride/ethyl acetate mixture as eluent gave 10, as a yellowsolid, m.p.: 140°-141°.

EXAMPLE 11 Tetrahydro-2-((2-(methoxycarbonyl)ethyl)nitromethylene)-2H-1,3-thiazine (11) Method D

A solution of 4.0 g of 1B and 2.5 g of methyl acrylate in 50 ml of1,2-dichloroethane was refluxed under nitrogen for 34 hours. Thereaction mixture was concentrated under reduced pressure andchromatographed through florisil with a 99:1 methylene chloride/methanolmixture as eluent to give a yellow solid. Recrystallization of the solidfrom ether/ethyl acetate/pentane mixture gave 10, as a pale yellowsolid, m.p.: 82°-83°.

EXAMPLE 12 ((2-cyanoethyl)nitromethylene)tetrahydro-2H-1,3-thiazine (12)Method D

A solution of 5.0 g of 1B and 1.8 g of acrylonitrile in 50 ml of1,2-dichloroethane was refluxed under nitrogen for 24 hours. Then 5.4 gof additional acrylonitrile was added and the mixture was refluxed for18 hours. Then 5.4 g of acrylonitrile was added and a further 5.4 gramswas added 4 hours later. The mixture was refluxed during this period andfor 18 hours thereafter. The mixture was concentrated under reducedpressure to leave a dark, gummy solid. The solid was chromatographed onflorisil using a 99:1 methylene chloride/methanol mixture as eluent togive two fractions: (a) yellow solid, m.p.: 135°-145°, and (b) yellowsolid, m.p.: 142°-151°. Fraction (a) was recrystallized from ethylacetate to give 12, as a yellow solid, m.p.: 144°-145°. Fraction (b) waswashed with ether to give more 12, as a yellow solid, m.p.: 142°-144°.

EXAMPLE 13 Tetrahydro-2 -(1-nitro-3-butenylidene)-2H-1,3-thiazine (13)Method G

A mixture of 16.0 of 1B and 100 ml allyl bromide was refluxed undernitrogen for 5 hours. After cooling, the mixture was diluted withmethylene chloride and washed with saturated sodium bicarbonate solutionand with water. The organic phase was dried (sodium sulfate) andconcentrated under reduced pressure to give a dark oil which waschromatographed on florisil using 99:1 methylene chloride/methanolmixture as eluent to give a red oil. Crystallization from ether gave 13as a light orange solid, m.p.: 55°-56°.

EXAMPLE 141,1,1-trichloro-3-nitro-3-(tetrahydro-2H-1,3-thiazin-2-ylidene)-2-propanol(14) Method H

4.0 g of chloral was added dropwise to a solution of 4.0 g of 1B in 50ml of methylene chloride. The solution was stirred at room temperatureunder nitrogen for 18 hours. Solid that formed was collected and washedwith methylene chloride to leave 14 as a pale yellow powder, m.p.:131°-131.5°.

EXAMPLE 15N,N-dimethyl-2-nitro-2-(tetrahydro-2H-1,3-thiazine-2-ylidine)ethanamine(15) Method I

5 g of 25% aqueous dimethylamine was added to a slurry of 4 grams of 1Bin 12 ml of ethanol. Then, with external cooling, 2.3 g of 37% aqueousformaldehyde was added at 24°-27°. The mixture then was stirred for 2hours at 25°, then was diluted with water and extracted with methylenechloride. The extract was dried and concentrated under reduced pressureto leave a yellow solid. This solid was washed with ether and air driedto give 15 as a yellow solid, m.p.: 100.5°-101°.

EXAMPLES 16 - 22

In a manner similar to that described in Example 15:

a. N,N-diethyl-2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethanamine(16) was prepared as a yellow solid, m.p.: 68°-69°;

b. tetrahydro-2-(1-nitro-2-(1-pyrrolidino)ethylidene)-2H-1,3-thiazine(17) was prepared as a pale yellow solid, m.p.: 102°-103°;

c. tetrahydro-2-(1-nitro-2-(1-piperidino)ethylidene)-2H-1,3-thiazine(18) was prepared as a pale yellow solid, m.p.: 115°-116°;

d. 4-(2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethyl)morpholine(19) was prepared as a pale yellow solid, m.p.: 131°-132.5°;

e.N-(2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)-N-(2-propenyl)-2-propen-1-amine(20) was prepared as a yellow solid, m.p.: 59°-61.5°;

f.N-(2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethyl)-N-phenylmethylbenzenemethanamine(21) was prepared as a pale yellow solid, m.p.: 108°-110.5°;

g.N-methyl-N-(2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethyl)benzenamine(22) was prepared as a yellow solid, m.p.: 105°-106.5°.

EXAMPLE 23 3-ethyltetrahydro-2-(nitromethylene)-2H-1,3-thiazine (23)

35 ml of tert-butyl lithium was added dropwise at -10° to a solution of8.0 g of 1B in 100 ml of tetrahydrofuran. The mixture was stirred for 5minutes at -10°, then 32 g of ethyl iodide was added at -5° to -15°, andthe mixture was stirred at -15° for 15 minutes. The mixture then waswarmed and stirred at room temperature for 24 hours, then stirred atreflux temperature for 24 hours, then cooled to 25°, 10 ml ofhexamethylphosphoramide added and the mixture stirred at refluxtemperature for 7 hours, then at room temperature overnight. Theresulting mixture was diluted with methylene chloride, the resultingsolution washed with saturated sodium chloride solution, dried and thesolvent evaporated under reduced pressure to give an amber oil. This oilwas chromotographed on silica gel, by dry column technique, using a40/8/2 mixture of hexane, ethyl acetate and tetrahydrofuran, to give 23as an amber oil, boiling point not determined.

EXAMPLE 24 tetrahydro-2-(1-nitro-3-butynylidene)-2H-1,3-thiazine (24)

A stirred mixture of 6 g of 1B, 30 ml of tertiary butyl alcohol and 30ml of propargyl bromide was heated to reflux for 3 hours, then wasallowed to stir at room temperature over a week-end, after which it washeated to reflux and stirred for 5.5 hours. The mixture then was cooled,diluted with methylene chloride, washed with saturated sodiumbicarbonate solution and water. The organic phase then was dried, andthe solvent evaporated under reduced pressure. The residue was passedthrough florisil, using methylene chloride as eluent, to give a gummyliquid, which when dissolved in isopropyl alcohol gave a brown solid,which on recrystallization from isopropyl alcohol gave 24, as a brownsolid, m.p.: 132°14 135°.

EXAMPLE 252-(2-(ethylthio)-1-nitroethylidene)-tetrahydro-2H-1,3-thiazine (25)

At 5°-10°, a solution of 1.75 g of ethanethiol in 5 ml of ethanol wasadded all at once to a mixture of 4.0 g of 1B in 50 ml of 50% ethanol.Then at 5°, 2.3 g of 37% aqueous formaldehyde was added dropwise and themixture stirred for 2 hours at 5° and at room temperature overnight. Itthen was poured into methylene chloride, the methylene chloride solutionwashed with saturated sodium chloride solution and the solventevaporated under reduced pressure. The resulting oil was passed throughflorisil, using a 99:1 methylene chloride/methanol mixture to give apale yellow solid, which was washed with ether to give 25, as a paleyellow solid, m.p.: 69.5°-71°.

EXAMPLE 262-(2-(ethylsulfinyl)-1-nitroethylidene)-tetrahydro-2H-1,3-thiazine (26)

A mixture of 2.34 g of 25 and 10 ml of acetone was added all at once toa solution of 2.25 g of sodium periodate in 15 ml of water. Theresulting exothermic reaction was controlled between 25° and 35° bycooling. The mixture then was stirred at room temperature for 90minutes, then was poured into a mixture of water and methylene chloride.The separated organic phase was washed with saturated sodium thiosulfatesolution, and saturated sodium chloride. It then was dried (MgSO₄) andthe solvent evaporated under reduced pressure to give an oil, which wastriturated with ether to give a yellow solid. This was chromatographedby a preparative thin layer chromatographic technique, on silica gel andusing a mixture of methanol (2%) in methylene chloride as eluent, togive 26, as a yellow solid, m.p.: 102°-104°.

EXAMPLE 27 Sodium Salt of 1B (27)

4.0 g of 1B was added to a solution of 1.0 g of sodium hydroxide in 25ml of water at room temperature. The resulting mixture was filteredthrough Celite to give 27, as an approximately one molar solution inwater.

EXAMPLE 28 HCl salt of 18 (28)

0.4 g of gaseous hydrogen chloride was bubbled into a mixture of 2.57 gof 18 in 50 ml of methylene chloride, at room temperature. The solventwas evaporated under reduced pressure. The residue was washed with etherand dried to give 28 as a tan solid, m.p.: 119°-121°.

EXAMPLES 29 - 31

By the procedure of Example 28 were prepared compounds, 29, 30 and 31,the HCl salts of:

a. 19, as a white solid, m.p.: 132.5°14 133°;

b. 15, as a tan solid, m.p.: 112.5°-113°;

c. 1B, as a beige solid, m.p.: 123°-125°;

EXAMPLE 32 methyl iodide salt of 18 (32)

A solution of 4.26 g of methyl iodide in 10 ml of ethanol was slowlyadded to a cold (5-10°) mixture of 5.14 g of 18 in 25 ml of ethanol,then 10 ml of methylene chloride was added. The mixture was stirred atroom temperature for 2.5 hours. Then 50 ml of ether was added, the solidwas collected and washed with additional ether to give 32, as a yellowsolid, m.p.: 120°14 121.5°.

EXAMPLE 33 2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethanol (33)

36.8 ml of 37% formaldehyde in water was added dropwise over a 30-minuteperiod to a slurry of 32 g of 1B in 120 ml of ethanol and 2 g oftriethylamine (as catalyst), at 5°-10°. 30 ml of ethanol and 20 ml ofwater were added to facilitate stirring and the mixture was stirredovernight. The solid which formed was separated by filtration and waswashed with ethanol and ether, then was dried in a vacuum oven to give33, as a light yellow solid, m.p.: 132°-133° (with decomposition).

EXAMPLE 34 tetrahydro-2-(nitro (phenylthio)methylene)-2H-1,3-thiazine(34)

7.2 g of benzenesulfenyl chloride in 25 ml of methylene chloride wasadded dropwise to 8.0 g of 1B and 5.1 g of triethylamine in 100 ml ofmethylene chloride at 0°-10° under an argon atmosphere. The cold mixturewas stirred for 30 minutes, then at room temperature for 1 hour. 300 mlof methylene chloride was added, the mixture washed with water and withsaturated sodium chloride solution. The separated organic phase wasdried and the solvent removed under reduced pressure. The residue waswashed with ethyl acetate to give 34, as a brown solid, m.p.: 144°-147°.

EXAMPLE 35

Tetrahydro-2-((4-methoxyphenylthio)-nitro-methylene)-2H-1,3-thiazine(35) was prepared as a yellow solid, m.p.: 160°-162°, from 1B and(4-methoxyphenyl)sulfenyl bromide according to the procedure of Example34.

EXAMPLE 362,2'-(1,3-dinitro-1,3-propanediylidene)bis-(tetrahydro)-2H-1,3-thiazine(36)

8 g of 1B, 6.6 ml of 37% formalin, 50 ml of methanol and 2 drops ofconcentrated sulfuric acid were mixed and the mixture heated in a steambath for 30 minutes. The mixture was cooled with ice and filtered togive 36,as a yellow solid, m.p.: 195°, with decomposition.

EXAMPLE 373-(tetrahydro-2-(nitromethylene)-2H-1,3-thiazin-2-yl)-2-propenoic acid,methyl ester (37)

4.2 g of methyl propiolate was added to a solution of 8 g of 1B in 50 mlof methanol at room temperature. After 2 hours, 5 drops of1,1,3,3-tetramethylguanidine was added. The reaction mixture temperaturerose to 36° after 1 hour. The solvent was evaporated under reducedpressure, and the residue was chromatrographed using ethyl acetate aseluent to give 37, as a yellow solid, m.p.: 128°-140°.

EXAMPLE 383-(tetrahydro-2-(nitromethylene)-2H-1,3-thiazin-2-yl)-2-propenoic acid,ethyl ester (38)

By the procedure described in Example 37, 38 was prepared as a yellowsolid, m.p.: 112°-120°.

EXAMPLE 39

By the general procedure described in Example 15,3,4-dichloro-N-(2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethybenzeneamine (39) was prepared, as a bright yellow solid, m.p.: 132°-133°, from1B, formaldehyde and 3,4-dichloroaniline.

EXAMPLE 402,4-dichloro-N-(2-nitro-2-(tetrahydro-2H-1,3-thiazin-2-ylidene)ethybenzeneamide (40)

3.9 g of 2,4-dichloroaniline was added, in several parts, to a solutionof 3.7 g of 33 in 25 ml of ethanol at 10°. The mixture was stirred for 2hours, being allowed to warm to room temperature. It then was stirredand heated gently, to 50°, for 1.5 hours. It then was allowed to stirovernight at room temperature. The solid product was separated byfiltration. It was washed with isopropyl alcohol, then with ether andair-dried. The residue was stirred in methylene chloride for 15 minutes.The mixture was filtered, the filtrate was washed with 5% sodiumhydroxide solution, then was dried and the solvent was evaporated togive 40, as a light yellow solid, m.p.: 122°-124°.

The compounds of this invention exhibit useful insecticidal activity,being of particular interest for control of the larvae "caterpillar" or"worm" forms of insects of the genus Heliothis, such as H. zea (cornearworm), cotton bollworm, tomato fruitworm), H. virescens (tobaccobudworm); the genus Agrotis, such as A. ipsilon (black cutworm); thegenus Trichoplusia, such as T. ni (cabbage looper), and the genusSpodoptera, such as S. littoralis (Egyptian cotton leafworm). Some arealso of interest for controlling whiteflies and houseflies. In teststhat have been conducted they have exhibited low, or no, toxicity toother insects such as the 2-spotted spider mite and mosquito larva. Someact very rapidly, providing "quick knock-down" of insects, in some caseseven though the compound is not very toxic to the insects.

Activity of compounds of this invention with respect to insects wasdetermined by using standardized test methods to establish the LC₅₀dosage (in milligrams of test compound per 100 milliliters of solvent orliquid carrier required in the solution of suspension of test compoundused) that was required to kill 50% of the test insects. The testinsects were the housefly, corn earworm, pea aphid and 2-spotted spidermite, and in some cases the black cutworm. Activity with respect tomosquito larvae was determined by placing the larvae in water containingthe test compound.

All of compounds 1A through 40 were found to be inactive or but slightlyactive with respect to the mites and mosquito larvae. With respect tothe corn earworm all of compound 1A - 40 were found to be active. Withrespect to the housefly, compounds 1A - 4, 7 - 10, 12 - 21, 24, 27 - 35and 37 were found to be active. With respect to the pea aphid compounds1A - 5, 7 - 10, 12 - 25, 27 - 34 and 36 - 38 were found to be active.Compounds 1 and 4 also were tested and found to be highly active withrespect to the black cutworm.

In the course of these tests it was noted that compounds, 4, 7 - 9, 13 -15, 18, 27, 32 and 33 acted very quickly on houseflies, compounds 1A, 8,12 - 14, 16, 21 - 22, 24, 27 and 29 - 33 acted very quickly on peaaphids and compounds 1A, 4, 7 - 9, 11 - 16, 18 - 21, 24, 27, 29, 31, 35and 36 acted very quickly upon corn earworms.

The invention includes within its scope insecticidal compositionscomprising an adjuvant -- that is, a carrier, optionally asurface-active agent -- and, as active ingredient, at least oneinsecticide of this invention. Likewise the invention includes also amethod a combatting insect pests at a locus which comprises applying tothe locus an effective amount of at least one insecticide of theinvention.

The term "carrier" as used herein means a material, which may beinorganic or organic and of synthetic or natural origin with which theactive compound is mixed or formulated to facilitate its application tothe plant, seed, soil and other object to be treated, or its storage,transport or handling. The carrier may be a solid or a liquid.

Suitable solid carriers may be natural and synthetic clays andsilicates, for example, natural silicas such as diatomaceous earths;magnesium silicates, for example, talcs; magnesium aluminum silicates,for example, attapulgites and vermiculites; aluminum silicates, forexample, kaolinites, montmorillonites and micas; calcium carbonate;calcium sulfate; synthetic hydrated silicon oxides and synthetic calciumor aluminum silicates; elements such as for example, carbon and sulfur;natural and synthetic resins such as, for example, coumarone resins,polyvinyl chloride and styrene polymers and copolymers; solidpolychlorophenols; bitumen; waxes such as beeswax, paraffin wax, andchlorinated mineral waxes; degradable organic solids, such as groundcorn cobs and walnut shells; and solid fertilizers, for example,superphosphates.

Suitable liquid carriers include solvents for the compounds of thisinvention and liquids in which the toxicant is insoluble or onlyslightly soluble.

Examples of such solvents and liquid carriers generally are water,alcohols, for example, isopropyl alcohol, ketones, such as acetone,methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers;aromatic hydrocarbons such as benzene, toluene and xylene; petroleumfractions, such as kerosene, light mineral oils, chlorinatedhydrocarbons, such as carbon tetrachloride, perchlorethylene,trichloroethane, including liquefied normally vaporous gaseouscompounds. Mixtures of different liquids are often suitable.

If used, the surface-active agent may be an emulsifying agent or adispersing agent or a wetting agent. It may be nonionic or ionic.Surface-active agents usually applied in formulating pesticides may beused. Examples of such surface-active agents are the sodium or calciumsalts of polyacrylic acids and lignin sulfonic acids; the condensationproducts of fatty acids or aliphatic amines or amides containing atleast 12 carbon atoms in the molecule with ethylene oxide and/orpropylene oxide; fatty acid esters of glycerol, sorbitan, sucrose orpentaerythritol; fatty acid salts of low molecular weight, mono-, di-and trialkylamines; condensates of these with ethylene oxide and/orpropylene oxide; condensation products of fatty alcohols or alkylphenols, for example, p-octylphenol or p-octylcresol, with ethyleneoxide and/or propylene oxide; sulfates or sulfonates of thesecondensation products; alkali or alkaline earth metal salts, preferablysodium salts, of sulfuric or sulfonic acids esters containing at least10 carbon atoms in the molecule, for example, sodium lauryl sulfate,sodium secondary alkyl sulfates, sodium salts of sulfonated cater oil,and sodium alkaryl sulfonates such as sodium dodecylbenzene sulfonate;and polymers of ethylene oxide and copolymers of ethylene oxide andpropylene oxide.

The compositions of the invention may be formulated as wettable powders,dusts, granules, solutions, emulsifiable concentrates, emulsions,suspension concentrates or aerosols. Encapsulated formulations andcontrolled release formulations also are contemplated, as are baitformulations. Wettable powders are usually compounded to contain 25, 50or 75%w of toxicant and usually contain, in addition to solid carrier,3-10%w of stabilizer (s) and/or other additives such as penetrants orstickers. Dusts are usually formulated as a dust concentrate having asimilar composition to that of a wettable powder but without adispersant, and are diluted in the field with further solid carrier togive a composition usually containing 1/2-10%w of toxicant. Granules maybe manufactured by agglomeration or impregnation techniques. Generally,granules will contain 1/2-25%w toxicant and 0-10%w of additives such asstabilizers, slow release modifiers and binding agents. Emulsifiableconcentrates usually contain, in addition to the solvent, and whennecessary, co-solvent, 10-50%w/v toxicant, 2-20%w/v emulsifiers and0-20%w/v of appropriate additives such as stabilizers, penetrants andcorrosion inhibitors. Suspension concentrates are compounded so as toobtain a stable, non-sedimenting, flowable product and usually contain10-75%w toxicant, 0-5%w of dispersing agents, 0.1-10%w of suspendingagents such as protective colloids and thixotropic agents, 0-10%w ofapropriate additives such as defoamers, corrosion inhibitors,stabilizers, penetrants and stickers, and as carrier, water or anorganic liquid in which the toxicant is substantially insoluble; certainorganic additives or inorganic salts may be dissolved in the carrier toassist in preventing sedimentation or an antifreeze agents for water.

Aqueous dispersions and emulsions, for example, compositions obtained bydiluting a wettable powder or an emulsifiable concentrate according tothe invention with water, also lie within the scope of the presentinvention.

The compositions of the invention may also contain other ingredients,for example, other compounds possessing pesticidal, herbicidal orfungicidal properties, or attractants, such as pheromones, attractivefood ingredients, and the like, for use in baits and trap formulations.

These compositions are applied in sufficient amount to supply theeffective dosage of toxicant at the locus to be protected. This dosageis dependent upon many factors, including the carrier employed, themethod and conditions of application, whether the formulation is presentat the locus in the form of an aerosol, or as a film, or as discreteparticles, the thickness of film or size of particles, the insectspecies to be controlled and the like, proper consideration andresolution of these factors to provide the necessary dosage of activematerial at the locus being within the skill of those versed in the art.In general, however, the effective dosage of toxicants of this inventionat the locus to be protected -- i.e. the dosage to which the insectcontacts -- is of the order of 0.001% to 0.5% based on the total weightof the fomulation, though under some circumstances the effectiveconcentration will be as little as 0.0001% or as much as 2%, on the samebasis.

I claim as my invention:
 1. A method for killing insects which comprises subjecting them to the action of an insecticidally effective amount of a compound selected from the group consisting of:1. a resonance hybrid in which the two significant forms which contribute thereto are represented by the formulae ##STR4## and including when R is hydrogen, the tautomeric form represented by the formula ##STR5## wherein R is hydrogen or contains up to eight carbon atoms and is one of: alkyl, alkeny;, alkoxyalkyl, cycloalkylalkyl, cyanoalkyl, haloalkenyl, phenalkyl or alkoxycarbonylvinyl;R¹ is hydrogen or contains up to eight carbon atoms and is one of a. alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, halo (hydroxy)alkyl, alkoxyalkyl, cyanoalkyl, hydroxyalkyl, alkoxycarbonylalkyl, alkylcarbonylalkyl,alkylthioalkyl, alkylsulfinylalkyl, phenalkyl or phenylthio optionally substialkyl, phenyl, alkoxy or phenoxy; b. halogen; c. aminomethyl, --CH₂ --NR² R³, wherein R² is alkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, alkenyl, phenyl or phenalkyl, and R³ is hydrogen or one of the moieties represented by R² ; d. (CH_(2n) --R⁴, wherein n is zero, one or two, and R⁴ is a heteromonocyclic moiety of from five to six atoms in the ring, containing in the ring carbon atoms and one to two of oxygen (--O--), sulfur (--S--) or nitrogen (═N-- or --NH--) bonded to carbon in the ring; and ##STR6##
 2. the alkali metal, alkyl halide, ammonium or amine salt of such a compound which R is hydrogen.
 2. A method according to claim 1 wherein R and R¹ each is hydrogen.
 3. A insecticidal composition comprising an insecticidally effective amount of a compound defined in claim 1, together with an insecticidal adjuvant therefor.
 4. A composition according to claim 3 wherein R and R¹ each is hydrogen. 